Overexpression of RNF187 induces cell EMT and apoptosis resistance in NSCLC

Abstract

Abstract Overexpression of RING finger protein 187 (RNF187) was recently revealed to be a driver of several cancers. However, the expression and function of RNF187 in non–small‐cell lung cancer (NSCLC) are still unknown. Here, we uncovered that RNF187 expression was significantly higher in NSCLC samples than in matched normal lung samples at both the messenger RNA (3.55 ± 0.79 vs. 1.74 ± 0.63) and protein (2.85 ± 0.14 vs. 1.24 ± 0.02) levels. By downregulating or upregulating RNF187 expression in NSCLC cells, we showed that elevated RNF187 expression distinctly enhanced the migration, invasion, and colony formation of NSCLC cells. Moreover, we revealed that high level of RNF187 promoted NSCLC progression by inducing cell epithelial to mesenchymal transition (EMT) and apoptosis resistance mainly via activating the mitogen‐activated protein kinase and PI3K signaling. Clinically, we demonstrated that RNF187 expression was positively associated with advanced TNM stage ( p = 1.29 × 10 −6 ), lymph node metastasis ( p = 2.69 × 10 −9 ), and large tumor size ( p = 0.002). Importantly, NSCLC patients with elevated RNF187 expression related to the short overall survival rate( p = 1.29, E‐7) and could serve as an independent prognostic factor in NSCLC patients. Thus, elevated RNF187 expression promotes NSCLC development by inducing cell EMT and apoptosis resistance, and RNF187 may be a novel prognostic indicator for NSCLC patients after curative resection.